Bostonia: The Boston University Alumni Magazine. Volume 32

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Quantum Physics and Human Language

Human languages employ constructions that tacitly assume specific properties of the limited range of phenomena they evolved to describe. These assumed properties are true features of that limited context, but may not be general or precise properties of all the physical situations allowed by fundamental physics. In brief, human languages contain `excess baggage' that must be qualified, discarded, or otherwise reformed to give a clear account in the context of fundamental physics of even the everyday phenomena that the languages evolved to describe. The surest route to clarity is to express the constructions of human languages in the language of fundamental physical theory, not the other way around. These ideas are illustrated by an analysis of the verb `to happen' and the word `reality' in special relativity and the modern quantum mechanics of closed systems.Comment: Contribution to the festschrift for G.C. Ghirardi on his 70th Birthday, minor correction

Bostonia: The Boston University Alumni Magazine. Volume 31

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Imagining an Imperial Modernity: Universities and the West African Roots of Colonial Development

© 2016 Informa UK Limited, trading as Taylor & Francis GroupThis article takes the formation and work of the ‘Elliot’ Commission on Higher Education in West Africa (1943–45) to reconsider the roots of British colonial development. Late colonial universities were major development projects, although they have rarely been considered as such. Focusing particularly on the Nigerian experience and the controversy over Yaba Higher College (founded 1934), the article contends that late colonial plans for universities were not produced in Britain and then exported to West African colonies. Rather, they were formed through interactions between agendas and ideas with roots in West Africa, Britain and elsewhere. These debates exhibited asymmetries of power but produced some consensus about university development. African and British actors conceptualised modern education by combining their local concerns with a variety of supra-local geographical frames for development, which included the British Empire and the individual colony. The British Empire did not in this case forestall development, but shaped the ways in which development was conceived

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis:a randomised, double-blind, placebo-controlled, phase 2b trial

Background: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods: We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings: Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation: Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials

A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis

Background: Cystic fibrosis (CF) is a chronic, life-limiting disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene leading to abnormal airway surface ion transport, chronic lung infections, inflammation and eventual respiratory failure. With the exception of the small-molecule potentiator, ivacaftor (Kalydeco®, Vertex Pharmaceuticals, Boston, MA, USA), which is suitable for a small proportion of patients, there are no licensed therapies targeting the basic defect. The UK Cystic Fibrosis Gene Therapy Consortium has taken a cationic lipid-mediated CFTR gene therapy formulation through preclinical and clinical development. Objective: To determine clinical efficacy of the formulation delivered to the airways over a period of 1 year in patients with CF. Design: This was a randomised, double-blind, placebo-controlled Phase IIb trial of the CFTR gene–liposome complex pGM169/GL67A. Randomisation was performed via InForm™ version 4.6 (Phase Forward Incorporated, Oracle, CA, USA) and was 1 : 1, except for patients in the mechanistic subgroups (2 : 1). Allocation was blinded by masking nebuliser chambers. Settings: Data were collected in the clinical and scientific sites and entered onto a trial-specific InForm, version 4.6 database. Participants: Patients with CF aged ≥ 12 years with forced expiratory volume in the first second (FEV1) between 50% and 90% predicted and any combination of CFTR mutations. The per-protocol group (≥ 9 doses) consisted of 54 patients receiving placebo (62 randomised) and 62 patients receiving gene therapy (78 randomised). Interventions: Subjects received 5 ml of nebulised pGM169/G67A (active) or 0.9% saline (placebo) at 28 (±5)-day intervals over 1 year. Main outcome measures: The primary end point was the relative change in percentage predicted FEV1 over the 12-month period. A number of secondary clinical outcomes were assessed alongside safety measures: other spirometric values; lung clearance index (LCI) assessed by multibreath washout; structural disease on computed tomography (CT) scan; the Cystic Fibrosis Questionnaire – Revised (CFQ-R), a validated quality-of-life questionnaire; exercise capacity and monitoring; systemic and sputum inflammatory markers; and adverse events (AEs). A mechanistic study was performed in a subgroup in whom transgene deoxyribonucleic acid (DNA) and messenger ribonucleic acid (mRNA) was measured alongside nasal and lower airway potential difference. Results: There was a significant (p = 0.046) treatment effect (TE) of 3.7% [95% confidence interval (CI) 0.1% to 7.3%] in the primary end point at 12 months and in secondary end points, including forced vital capacity (FVC) (p = 0.031) and CT gas trapping (p = 0.048). Other outcomes, although not reaching statistical significance, favoured active treatment. Effects were noted by 1 month and were irrespective of sex, age or CFTR mutation class. Subjects with a more severe baseline FEV1 had a FEV1 TE of 6.4% (95% CI 0.8% to 12.1%) and greater changes in many other secondary outcomes. However, the more mildly affected group also demonstrated benefits, particularly in small airway disease markers such as LCI. The active group showed a significantly (p = 0.032) greater bronchial chloride secretory response. No difference in treatment-attributable AEs was seen between the placebo and active groups. Conclusions: Monthly application of the pGM169/GL67A gene therapy formulation was associated with an improvement in lung function, other clinically relevant parameters and bronchial CFTR function, compared with placebo. Limitations: Although encouraging, the improvement in FEV1 was modest and was not accompanied by detectable improvement in patients’ quality of life. Future work: Future work will focus on attempts to increase efficacy by increasing dose or frequency, the coadministration of a CFTR potentiator, or the use of modified viral vectors capable of repeated administration. Trial registration: ClinicalTrials.gov NCT01621867. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research partnership